The current success in the management of AIDS, resulting in reduction of HIV viral load, increase in CD4 count, and reduced morbidity and mortality due to opportunistic infections, has raised concern about the necessity for the continuation of antimicrobial prophylaxis after patients have reverted CD4 cell counts to levels that would disqualify them by present-day guidelines for PCP and MAC prophylaxis. It is reasonable to expect that such patients no longer need antimicrobial prophylaxis and such data are now being collected and analyzed in adults with HIV infection. However, similar data in a comparable population of HIV-infected children and adolescents are not yet available on which to base such a practice. Additionally, serious bacterial infections are an important factor to account for when considering the impact of discontinuing PCP and MAC prophylaxis. This is because of the beneficial collateral effect of PCP and MAC prophylactic regimens on the prevention of infectious complications of HIV disease in children. ACTG 254, which compared prophylaxis drug regimens, provides a unique database from which a historical cohort can be developed. This cohort would provide an opportunity to determine if opportunistic infection prophylaxis can be safely withdrawn after immune reconstitution so patients are no longer in the well-established high risk groups.